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Acquired resistance of MET-amplified non-small cell lung cancer cells to the MET inhibitor capmatinib
DC Field | Value | Language |
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dc.contributor.author | Kim, Seulki | - |
dc.contributor.author | Kim, Tae Min | - |
dc.contributor.author | Kim, Dong-Wan | - |
dc.contributor.author | Kim, Soyeon | - |
dc.contributor.author | Kim, Miso | - |
dc.contributor.author | Alm, Yong-Oon | - |
dc.contributor.author | Keam, Bhumsuk | - |
dc.contributor.author | Heo, Dae Seog | - |
dc.date.accessioned | 2020-04-27T11:00:50Z | - |
dc.date.available | 2020-04-27T11:00:50Z | - |
dc.date.created | 2019-08-20 | - |
dc.date.issued | 2019-07 | - |
dc.identifier.citation | Cancer Research and Treatment, Vol.51 No.3, pp.951-962 | - |
dc.identifier.issn | 1598-2998 | - |
dc.identifier.other | 81441 | - |
dc.identifier.uri | https://hdl.handle.net/10371/165223 | - |
dc.description.abstract | Purpose Amplified mesenchymal-epithelial transition factor, MET, is a receptor tyrosine kinase (RTK) that has been considered a druggable target in non-small cell lung cancer (NSCLC). Although multiple MET tyrosine kinase inhibitors (TKIs) are being actively developed for MET-driven NSCLC, the mechanisms of acquired resistance to MET-TKIs have not been well elucidated. To understand the mechanisms of resistance and establish therapeutic strategies, we developed an in vitro model using the MET-amplified NSCLC cell line EBC-1. Materials and Methods We established capmatinib-resistant NSCLC cell lines and identified alternative signaling pathways using 3' mRNA sequencing and human phospho-RTK arrays. Copy number alterations were evaluated by quantitative polymerase chain reaction and cell proliferation assay; activation of RTKs and downstream effectors were compared between the parental cell line EBC-1 and the resistant cell lines. Results We found that EBC-CR1 showed an epidermal growth factor receptor (EGFR)-dependent growth and sensitivity to afatinib, an irreversible EGFR TKI. EBC-CR2 cells that had overexpression of EGFR-MET heterodimer dramatically responded to combined capmatinib with afatinib. In addition, EBC-CR3 cells derived from EBC-CR1 cells that activated EGFR with amplified phosphoinositide-3 kinase catalytic subunit alpha (PIK3CA) were sensitive to combined afatinib with BYL719, a phosphoinositide 3-kinase alpha (PI3K alpha) inhibitor. Conclusion Our in vitro studies suggested that activation of EGFR signaling and/or genetic alteration of downstream effectors like PIK3CA were alternative resistance mechanisms used by capmatinib-resistant NSCLC cell lines. In addition, combined treatments with MET, EGFR, and PI3K alpha inhibitors may be effective therapeutic strategies in capmatinib-resistant NSCLC patients. | - |
dc.language | 영어 | - |
dc.publisher | 대한암학회 | - |
dc.title | Acquired resistance of MET-amplified non-small cell lung cancer cells to the MET inhibitor capmatinib | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 김동완 | - |
dc.contributor.AlternativeAuthor | 허대석 | - |
dc.identifier.doi | 10.4143/crt.2018.052 | - |
dc.citation.journaltitle | Cancer Research and Treatment | - |
dc.identifier.wosid | 000476707300011 | - |
dc.identifier.scopusid | 2-s2.0-85065306468 | - |
dc.citation.endpage | 962 | - |
dc.citation.number | 3 | - |
dc.citation.startpage | 951 | - |
dc.citation.volume | 51 | - |
dc.identifier.sci | 000476707300011 | - |
dc.identifier.kciid | ART002486336 | - |
dc.description.isOpenAccess | Y | - |
dc.contributor.affiliatedAuthor | Kim, Dong-Wan | - |
dc.contributor.affiliatedAuthor | Heo, Dae Seog | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | GROWTH-FACTOR RECEPTOR | - |
dc.subject.keywordPlus | C-MET | - |
dc.subject.keywordPlus | GENE AMPLIFICATION | - |
dc.subject.keywordPlus | KINASE INHIBITOR | - |
dc.subject.keywordPlus | TUMOR-GROWTH | - |
dc.subject.keywordPlus | COPY NUMBER | - |
dc.subject.keywordPlus | CROSS-TALK | - |
dc.subject.keywordPlus | MUTATIONS | - |
dc.subject.keywordPlus | EGFR | - |
dc.subject.keywordPlus | HETERODIMERIZATION | - |
dc.subject.keywordAuthor | MET tyrosine kinase inhibitor | - |
dc.subject.keywordAuthor | Capmatinib | - |
dc.subject.keywordAuthor | MET amplification | - |
dc.subject.keywordAuthor | Non-small cell lung carcinoma | - |
dc.subject.keywordAuthor | Acquired resistance | - |
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